Nucleolin is a predominant nucleolar protein in growing eukaryotic cells, primarily associated with intranucleolar chromatin and pre-ribosomal particles. Its key functions include:

• Chromatin Decondensation: Induces chromatin decondensation by binding to histone H1.
• Ribosome Assembly: Plays a role in pre-rRNA transcription and ribosome assembly.
• Transcriptional Elongation: May be involved in the process of transcriptional elongation.
• RNA Binding: Binds RNA oligonucleotides with 5’-UUAGGG-3’ repeats more tightly than telomeric single-stranded DNA with 5’-TTAGGG-3’ repeats.

This protein is a key component of messenger ribonucleoprotein particles (mRNPs) and plays a crucial role in the regulation of germ cell mRNA stability and translation. Its functions include:

• mRNA Binding: Binds full-length mRNA with high affinity in a sequence-independent manner and binds short RNA sequences with low affinity.
• Y-box Interaction: Binds to the Y-box consensus promoter element, potentially marking mRNAs for cytoplasmic storage.
• Cytoplasmic Retention: Essential for the cytoplasmic retention of maternal mRNAs.
• mRNA Storage: May link transcription and mRNA storage/translational delay by marking specific mRNAs for cytoplasmic storage.

This gene encodes a subunit of the U1 snRNP (small nuclear ribonucleic particle), one of at least five snRNPs to comprise the spliceosome, which functions in processing of pre-mRNAs. The U1 snRNP has been shown to be important in defining the 5’ splice site. Alternative splicing results in multiple transcript variants

This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm.

Enables RNA binding activity. Involved in several processes, including cell cycle switching, mitotic to meiotic cell cycle; meiotic nuclear division; and spermatid differentiation. Acts upstream of or within mRNA stabilization and trophectodermal cell differentiation. Located in cytoplasm and nucleus. Is expressed in central nervous system; craniocervical region bone; dorsal root ganglion; lung; and rib. Orthologous to human RBM46

Splicing factor, which binds the consensus motif 5’-C[ACU][AU]C[ACU][AC]C-3’ within pre-mRNA and promotes specific exons inclusion during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites within exons. Also functions as an adapter involved in mRNA nuclear export. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export

This protein is a member of the eIF2 complex, playing a crucial role in the early steps of protein synthesis and stress response. Key functions include:

• Protein Synthesis Initiation: Forms a ternary complex with GTP and initiator tRNA, binding to the 40S ribosomal subunit to form the 43S pre-initiation complex, and later the 80S initiation complex after GTP hydrolysis.
• GTP/GDP Exchange: Requires GDP-GTP exchange, catalyzed by eIF2B, for recycling and initiating another round of protein synthesis.
• Integrated Stress Response (ISR): Phosphorylation by stress-sensing kinases turns eIF2-alpha into an inhibitor of global protein synthesis, reducing cap-dependent translation while promoting translation of ISR-specific mRNAs like ATF4 and QRICH1.
• Mitophagy Activation: Acts as an activator of mitophagy in response to mitochondrial damage by relocating to the mitochondrial surface upon phosphorylation, triggering PRKN-independent mitophagy.

• DNA and RNA Binding: Enables sequence-specific DNA binding at RNA polymerase II cis-regulatory regions and binds pre-mRNA introns.
• Regulatory Roles: Involved in positively regulating protein import into the nucleus, circadian rhythm, and protein stability.
• RNA Splicing: Acts upstream of or within RNA splicing processes.
• Localization and Expression: Located in the nucleus and expressed in various structures, including the central nervous system, heart, genitourinary system, branchial arch, and early conceptus.
• Research and Disease Study: Used in studies related to Grn-related frontotemporal lobar degeneration with TDP-43 inclusions, amyotrophic lateral sclerosis type 10, and frontotemporal dementia.
• Human Orthologs: The human ortholog, TARDBP, is implicated in Parkinson’s disease, amyotrophic lateral sclerosis, and motor neuron disease.

• RNA Binding: Predicted to enable RNA binding activity.
• Circadian Regulation: Involved in the circadian regulation of gene expression and the entrainment of the circadian clock by photoperiod.
• Translation Regulation: Plays a role in the regulation of translation.
• Gene Expression: Acts upstream of or within the positive regulation of gene expression.
• Cellular Localization: Predicted to be located in the cytosol and nucleoplasm and active in nuclear specks.
• Complex Participation: Predicted to be part of a protein-containing complex.
• Expression: Expressed in various systems, including the alimentary, brain, cardiovascular, genitourinary, and hemolymphoid systems.

Predicted to enable RNA binding activity and identical protein binding activity. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. Is expressed in brain; cortical plate; spinal cord; and trigeminal ganglion

• Alternative Splicing: Involved in alternative pre-mRNA splicing, particularly activating splicing of exons with weak 5’ splice sites followed by a U-rich stretch, including its own pre-mRNA and TIA1 mRNA.
• RNA Preference: Shows a preference for binding uridine-rich RNAs.
• Exon Inclusion: Promotes the inclusion of exon 5 in TIA1, leading to the production of the long isoform (isoform a) of TIA1.
• Stress Granules Formation: Plays a role in forming cytoplasmic stress granules, acting downstream of stress-induced EIF2S1/EIF2A phosphorylation to recruit untranslated mRNAs to these granules.

• RNA Binding: Binds to the cytoplasmic polyadenylation element (CPE), a uridine-rich sequence in the mRNA 3’-UTR, causing a conformational change similar to the Venus fly trap mechanism.
• ER Stress Response: Regulates the activation of the unfolded protein response (UPR) during ER stress in the liver by maintaining the translation of CPE-regulated mRNAs when global protein synthesis is inhibited.
• Cell Cycle and Cytokinesis: Essential for cell cycle progression, particularly cytokinesis and chromosomal segregation.
• Oncogenic Role: Acts as an oncogene by promoting tumor growth and progression through the positive regulation of t-plasminogen activator/PLAT translation.
• Melanocyte Proliferation: Stimulates the proliferation of melanocytes.
• Synaptic Plasticity: Unlike CPEB1 and CPEB3, it does not play a role in synaptic plasticity, learning, and memory.

• Gene Transcription and Tumor Suppression: Binds to and stimulates transcription from the TXNIP gene promoter, potentially playing a role in tumor suppression. When associated with SAFB, it also stimulates transcription from the SREBF1 promoter.
• mRNA Association: Associates with nascent mRNAs transcribed by RNA polymerase II and is part of the supraspliceosome complex, influencing pre-mRNA alternative splice site selection.
• Alternative Splicing: Can activate or suppress exon inclusion; works with TRA2B to promote exon 7 inclusion in SMN2 and represses the splicing of MAPT/Tau exon 10.
• RNA Binding: Binds preferentially to single-stranded 5’-CC[A/C]-rich RNA sequence motifs and likely binds RNA as a homodimer. It also binds non-specifically to pre-mRNAs.
• Cytoplasmic Role: Involved in cytoplasmic TNFR1 trafficking, promoting IL-1-beta-mediated cleavage of TNFR1 ectodomains and the release of TNFR1 in exosome-like vesicles.

• Binding Specificity: Prefers binding to oligo dC and also binds poly(rC) and poly(rU).
• Antiviral Signaling Regulation: Acts as a negative regulator of antiviral signaling, specifically by:
• MAVS Signaling: Serving as an adapter between MAVS and the E3 ubiquitin ligase ITCH, facilitating MAVS ubiquitination and degradation.
• cGAS-STING Pathway: Interacting with CGAS to prevent the formation of liquid-like droplets necessary for CGAS activation.
• Erythropoiesis: Along with PCBP1, it is required for erythropoiesis, possibly through the regulation of mRNA splicing.

Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be involved in epithelial structure maintenance. Predicted to be located in Golgi apparatus. Predicted to be active in cytoplasm. Is expressed in Meckel’s cartilage; chondrocranium; and olfactory epithelium.